Antroduodenal motor function and gastro-oesophageal reflux in neurologically impaired children, adolescents and young adults.
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Biomedical subjects
Publications and source records attributed to H Tajiri.
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BACKGROUND/AIMS: We investigated the efficacy of interferon therapy for the treatment of children with chronic hepatitis C virus infection. METHODS: Twenty-four out of 26 children completed the 6-month treatment with lymphoblastoid interferon-alpha and were followed for 12 months or longer. Response to interferon therapy was defined by assaying for circulating HCV-RNA, using a nested PCR, at 6-month intervals after the end of the therapy. RESULTS: At the end of treatment circulating HCV-RNA was undetectable in 18/24 patients and at 6 months in 12/24. Ten of these 12 primary responders have remained virus free for more than 2 years. One patient remained negative at 12 months. The remaining patient relapsed at 12 months. At 24 months 10 of 18 patients tested negative for HCV-RNA. Serum alanine aminotransferase was normal in 11/24 patients at the end of treatment, at 6 months 12/24 were normal, and at 12 months 11/12 were normal. In eight children with sustained response, repeated liver biopsies revealed a reduction in Knodell's scores for inflammation in the hepatic lobules and in the portal areas. In three of them neither plus nor minus strand of HCV-RNA was detectable in the liver tissue. Responders had a significantly lower level of viremia than non-responders. Side effects of interferon including fever, hair loss, neutropenia, and thrombocytopenia were not serious enough to warrant cessation of interferon treatment. CONCLUSIONS: Interferon therapy in children with chronic hepatitis C may be beneficial as evaluated by sustained loss of viremia as well as by primary response.
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Small advanced cancers (less than 10 mm in size) have rarely been described in the literature, mainly due to their difficult endoscopic diagnosis. A total of 5120 colonoscopic examinations were performed at the National Cancer Center Hospital East; three cases (0.05%) of small advanced cancer were found. The indigo carmine dye spraying technique with magnifying endoscopy was used for diagnosis. All cases were flat and depressed lesions (8, 9 and 9 mm in size respectively) with V type pit pattern at the magnifying observation. Histology showed three cancers with invasion to the proper muscle layer and two cases of lymph node metastasis. K-ras point mutation was negative in all cases, while p53 stained in two out of the three cases (one diffuse and one focal). It is concluded that small advanced colorectal adenocarcinomas are a reality. Our data on their macroscopic appearance and histology confirm their high malignant potential.
Hereditary nonpolyposis colorectal cancer is an autosomal, dominantly inherited disease, characterized by an early age of onset, right colon predominance and an association with various extracolorectal malignancies. We present a case of a 47-year-old woman who met the clinical criteria for the diagnosis of hereditary nonpolyposis colorectal cancer from her past and family histories. She had undergone operations for uterine cancer (histology not confirmed) at age 35 and for advanced cancer of the ascending colon at age 45. Gastroendoscopy revealed a flat elevated lesion, 20 mm in size, with a protrusion (type IIa + Is) in the second portion of the duodenum in March 1996. Additionally, colonoscopy showed a flat elevated lesion, 30 mm in size, with an irregular and nodular surface (type IIa, laterally spreading tumor) in the descending colon. After the operation, the resected specimen of the duodenum histologically showed a well-differentiated adenocarcinoma associated with a tubulo-villous adenoma which had invaded the submucosal layer. The tumor of the colon was histologically confirmed to be a moderately-differentiated adenocarcinoma with submucosal invasion. A high frequency of replication error positivity (4/5 loci) was detected in both of the tumors. Reports of early cancer of the duodenum, associated with extracolorectal malignancies in hereditary nonpolyposis colorectal cancer, are very rare in the literature. Although it is difficult to determine which extracolorectal tumor sites should be taken into consideration by screening programs, we believe that careful observation by upper gastrointestinal endoscopy, which includes the duodenum, is necessary for patients with hereditary nonpolyposis colorectal cancer.
BACKGROUND: A prospective study was carried out to clarify the efficacy of an endoscopic screening program for detecting superficial colorectal neoplasias by color changes such as faint redness or discoloration, which have been described as a key finding of these lesions in the literature. METHODS: We enrolled 716 consecutive cases in this study, but more than half of them did not reveal any abnormalities colonoscopically. RESULTS: Of the 716 cases, 48 (7%) were examined by magnifying colonoscopy with a dye spraying technique, following the detection of superficial color changes. Sixteen neoplastic lesions (in 16 cases) were detected among the 48 cases and the detection rate was calculated as 2.2% (16/716) in the total number of cases and 33% (16/48) in those showing color abnormalities. Histologically, all of the 16 were adenomas. These neoplastic lesions were most frequent (52%; 11/21) in those showing faint redness in an oval shape, whereas 14 (94%) of the 15 lesions were non-specific in those showing faint redness with unclear margin. CONCLUSIONS: These results may confirm the diagnostic utility of color abnormality, particularly faint redness in an oval shape, for endoscopic screening of superficial colorectal neoplasias.
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The efficacy associated with peroral pancreatoscopy to diagnose and differentiate pancreatic diseases is herein reviewed and clarified, and problems with this modality are discussed. Three types of pancreatoscopes are presently available: (a) a thin fiberscope with a diameter of 3.3 or 4.5 mm, which has an angulation system and a forceps channel; (b) an ultrathin pancreatoscope with a diameter of 0.75 or 0.8 mm, which can be inserted via an ordinary endoscopic retrograde cholangiopancreatography (ERCP) cannula without endoscopic sphincterotomy; and (c) an ultrathin pancreatoscope combined with a catheter that has an outer diameter of 1.67 mm. Peroral pancreatoscopy facilitates the detection of small lesions of the duct in malignancy or chronic pancreatitis. In particular, it is quite useful in differentiating pancreatic cancer from chronic pancreatitis in cases with local stenosis or elevated lesions of the main pancreatic duct. Among patients with a mucus-producing tumor of the pancreas, pancreatoscopy is also very useful, especially in determining lesion extent. Despite some unresolved problems, we predict that pancreatoscopy will retain a limited or specific and definite role in diagnostic and therapeutic endoscopy for pancreatic diseases.
An infant born prematurely and infected with hepatitis C virus (HCV) one month after birth was followed for 4.5 years. The patient did not produce detectable anti-HCV antibodies until two years after the onset of hepatitis. Before seroconversion, a single clone of HCV, as determined by quasispecies of the hypervariable region (HVR) of the HCV genome, was almost exclusively found in the serum. After seroconversion, however, another distinct lineage of HCV clones replaced it within half a year. As HCV infection persisted further in the presence of anti-HCV antibodies, many derivatives of both sequence lineages emerged to exhibit the typical quasispecies feature of HVR sequences. Neither seroconversion nor the changes in HVR sequences influenced the serum aminotransferase titers.
We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum gamma-glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohn's colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.
This report concerns an 11-year-old boy who manifested hypophosphatemic rickets associated with congenital microvillous atrophy (CMA). He had been suffering from vomiting and severe diarrhea from the first day of life and had been treated with total parenteral nutrition (TPN) since he was 67 days old. At 4 years of age, intestinal biopsy resulted in a diagnosis of CMA. He was admitted to our hospital complaining of leg pain at the age of 11. Laboratory data revealed hypophosphatemia, elevated serum 1, 25-dihydroxyvitamin D (1,25(OH)2D) levels, and hypercalciuria. A roentgenogram showed rickets in the extremities. A balance study of phosphate in urine and stool indicated that the amount of phosphate leaking into the stool was greater than that into the urine. Moreover, the total amount of phosphate leaking from both the intestine and kidney exceeded the amount of phosphate intake from TPN. The rickets was healed by increasing the phosphate concentration in TPN. This case is different from X-linked hypophosphatemic rickets but similar to hereditary hypophosphatemic rickets with hypercalciuria (HHRH) in terms of hypercalciuria and elevated serum 1,25(OH)2D levels. The effectiveness of phosphate treatments used here is also similar to that used for HHRH. However, this type of hypophosphatemic rickets is unique in that phosphate leaking into the intestine plays an important role in its pathogenesis.
Congenital chloride diarrhea (CLD) is an autosomal recessive disease characterized by excretion of watery stool with a high chloride content. Pathogenesis of CLD is a deficient absorption of chloride in exchange for bicarbonate in the ileum and the colon. In 1996, it was reported that 36 patients with CLD had mutations in the down-regulated in adenoma (DRA) gene; 32 Finnish patients had a three base deletion (951delGGT), 2 Polish patients had a one base mutation (371AtoT) and 2 Polish patients had a one base deletion (344delT). In this study we analyzed the DRA gene in a Japanese boy patient with CLD and in members of his family. The patient was found to have a two base deletion (TT) at nucleotide 1526-1527 within codon 509 which results in a frameshift leading to a permature stopping at codon 517. The patient was homozygous for the deletion, his parents and brother were heterozygous, and his sister was normal. This is the first case of CLD identified to carry a mutation of the DRA gene in Asia.
We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.
We evaluated the effect of nitric oxide (NO) on vascular endothelial growth factor (VEGF) gene expression in human A-172 glioblastoma cells and human HepG2 hepatocellular carcinoma cells. The mRNA level of VEGF increased in response to S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) in both cell lines, and increased in mRNA level well coincided with VEGF protein production in A-172 cells. SNAP at 0.5 mM induced maximal stimulation of 4.4 and 3.7 kb VEGF mRNA expression after 6 h about 11 and 8 fold increase, respectively above control level. Similar VEGF mRNA accumulation was observed also with NOR3, another chemical NO generator. To evaluate the effect of SNAP on VEGF mRNA stability, half-lives of VEGF mRNA were measured in A-172 cells cultured with or without 0.5 mM SNAP and treated with actinomycin D (25 microg/ml). Half-life for VEGF mRNA was found to be prolonged about 2.4 fold by SNAP. VEGF expression induced by SNAP was inhibited by guanylate cyclase inhibitors, methylene blue (10 microM) and LY-83583 (1 microM), and by the protein synthesis inhibitor, cycloheximide (25 microg/ml). These results suggest that induction of VEGF gene expression by NO is mediated through guanylate cyclase activity and requires on-going protein synthesis.
To clarify the usefulness of fluorescent diagnosis for gastric cancer, we assessed the sensitivity and specificity of the tumor-localizing photochlorine photosensitizer ATX-S10 in combination with a new fluorescence diagnostic system. Into the submucosa of the stomachs of five rabbits, VX-2 tumor cells originating from squamous cell carcinoma were injected. After 3 weeks, three rabbits (Group I) were sacrificed 3 h after intravenous injection of ATX-S10 at a dose of 20 mg/kg, and their stomachs were observed by the Hg-lamp-induced fluorescence diagnostic system. The other two rabbits (Group II) were also sacrificed without injection of ATX-S10 and observed by the same method. In all cases in Groups I and II, gastric cancers that were invaded from the submucosa to the serosa were recognized histologically. The concentration of ATX-S10 examined by high-performance liquid chromatography (HPLC) in the gastric cancer was significantly higher than in the normal stomach. Fluorescent spectroscopy could detect 630 nm fluorescence selectively, consistent with the cancerous tissue of Group I. Moreover, fluorescent images were detected in only the exposed area of cancerous tissue and were undetected in the surrounding normal mucosa. Conversely, no fluorescent images could be detected in the stomachs of Group II. It is suggested that a fluorescence diagnostic system using ATX-S10 may become useful for the diagnosis of the existence or extension of carcinoma of the gastrointestinal tract.
Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.
CONCLUSION: These data show that pure pancreatic juice of AICP patients has a markedly defective antibacterial activity. This finding might be of potential clinical interest in the understanding of the pathophysiology of the disease. BACKGROUND: The aim of the present study was to test the antibacterial activity of pure pancreatic juice in patients with chronic pancreatitis. METHODS: The study group consisted of ten patients with ethanol-induced chronic pancreatitis (AICP) and seven control patients free of pancreatic disease. All subjects had recently undergone a secretin-pancreozymin pancreatic function test. After an overnight fast, through a side-viewing endoscope, selective pancreatic duct cannulation was performed. After secretin stimulation, pure pancreatic juice was obtained. Three fractions of different molecular weights were separated. Samples were incubated with 1-mL suspension of 10(5) Escherichia coli ATCC 25,922, and log10 of colony-forming units were counted. Experiments were repeated by grading pancreatic juice concentration, pH of the medium, and inoculum size. RESULTS: No significant change of pH of pure pancreatic juice appeared between AICP and controls. Starting from 6-h observation, pure pancreatic juice of AICP patients showed a significant bacterial colonization vs controls (p < 0.01). A direct correlation appeared between bacterial colonization and either pH and dilution of pancreatic juice (p < 0.001). Antibacterial activity was independent of inoculum size, enzymatic activation or inhibition, and heat treatment. The fraction with 1000-10,000 molecular weight was the one endowed with antibacterial activity.
A 20-month-old boy was investigated for persistent liver dysfunction. Liver histologic findings showed chronic hepatitis. The presence of human herpesvirus-6 DNA in liver tissue was demonstrated both by in situ hybridization and by polymerase chain reaction. Human herpesvirus-6 may be a causative agent of chronic hepatitis in this case.